Investigations of systemic lupus erythematosus (SLE) will be undertaken in three species: mice, dogs and humans. A unique colony of dogs with autoimmune diseases will be maintained for study and developed further. Three hypotheses about SLE will be tested: (1) A retravirus contributes to the disease in dogs and humans. (2) Household contracts between humans and dogs can be implicated in the etiology of SLE. (3) Defective immunoregulation is a primary, genetically determined abnormality in SLE. (4) A dual system of cooperating genes is implicated in the pathogenesis of SLE.